Epidemiology

The prevalence of vulvar lichen sclerosus (VLS) in the general population is not known. Wallace estimated that “the frequency in a general hospital varied from 1 in 300 of all new patients to less than to 1 in 1000 patients depending on the liaison between skin and gynaecological departments.” The majority of the patients with VLS are over 50 years of age. In a study including 327 patients, 60% were post-menopausal and the mean age at diagnosis was 60 . However, women in their reproductive age as well as girls may be affected.

Aetiology

Lichen sclerosus (LS) is a chronic non-neoplastic, non-infectious, inflammatory skin disorder with a predilection for the genital area. The condition is currently considered as an autoimmune disorder occurring in genetically predisposed patients. In a cohort of 190 patients, 28.4% had at least one autoimmune condition . In agreement with previous studies , this study showed that thyroid disease was significantly more frequent in patients with VLS (16.3% vs. 7.9%) than in controls. Other conditions such as alopecia areata, morphea and pernicious anaemia are less significantly associated. Immunoglobulin G (IgG) autoantibodies targeting extracellular matrix 1(ECM1) protein have been found in 74% of women with genital LS compared with 7% in controls , and glycoprotein ECM1 seems to be significantly more expressed in VLS than in controls .

A genetic predisposition was shown in an observational cohort study of 1052 women with VLS where 12% had a family history of LS . HLA-DR and DQ antigens or their haplotypes appear to be involved in susceptibility or resistance to VLS.

Pathology

LS is histologically characterized by both epidermal and dermal features. The atrophic thinned horizontal epithelium is covered by a compact ortho-hyperkeratosis. Basal vacuolar alteration is often present. One of the most striking features is the presence of a wide band of hyalinization located in the upper dermis, just beneath the dermo-epidermal junction and underlined by a lymphocytic infiltrate. The histological features of LS may vary according to the stage of the disease. In its burnt-out stage, a pathological diagnosis may be very difficult to achieve.

Symptoms

In adults, VLS is classically responsible for itching, burning or introital dyspareunia, whereas in girls itching, dysuria, bleeding and constipation are reported . However, VLS may cause no symptoms and may be discovered during a routine gynaecological examination or when a complication such a squamous cell carcinoma (SCC) occurs. The rate of asymptomatic VLS is not known.

Signs

VLS mainly affects the labia minora, the internal sides of the labia majora, the clitoris and the perineum. Anal involvement is associated in about one third of the cases . Extragenital LS (mainly back, chest, proximal extremities and thighs) was observed in 18.7% of 396 women with anogenital LS .

The most common features of VLS are pallor, textural changes and architectural modifications which are diversely associated according to the patients and to the stage of the condition ( Figs. 1 and 2 ). Pallor may be widespread or circumscribed and may have a perifollicular display. The pale areas may be either unruffled or wrinkled. Architectural modifications also designated as ‘scarring’ result from adhesions (synechiae) between two contiguous surfaces involved by LS. The clitoral glans may get sealed under the hood whereas there is a shrinkage or even a loss of the labia minora. Internal synechiae of the labia minora may lead to an introital narrowing responsible for dyspareunia.

Vulvar Lichen sclerosus: Pallor, scarring (loss of labia minora and sealing of the clitoris), ecchymosis.

Vulvar Lichen Sclerosus: pallor, atrophy (wrinkled aspect on the perineum) and perineal fissures.

Other features of VLS include fissures, erosions, ecchymosis, pigmentation and epidermoid clitoral cyst. Ecchymoses are almost pathognomonic of genital LS. In girls, these violaceous macules should not be misinterpreted as a result of sexual abuses .

Differential diagnosis

The differential diagnoses of VLS are shown in Table 2 .

Evolution

The natural history of VLS is not well known. The condition is chronic, with a relapsing and remitting course. In a study of 83 women with VLS, the cumulative incidence of relapse after ending treatment was estimated at 50% at 16 months and 84% at 4 years . Although VLS is, for a vast majority of the patients, a benign condition, complications may occur. Infections such as candidosis, herpes or human papillomavirus (HPV)-related lesions are facilitated by the treatments with topical corticosteroids (TCS). Exceptionally, VLS turns into SCC. SCC precursors have been identified. Differentiated vulvar intraepithelial neoplasia (dVIN) is characterized by basal and suprabasal epithelial architectural and cytological atypia. It should be suspected if there is any circumscribed lesion resisting to ultrapotent topical corticosteroids (UPTCS): white raised lesions or pink patches. It has a high malignant potential and tends to recur after excision. Usual-type VIN is more rarely observed in the periphery of SCC than dVIN . Acanthotic lesions usually present as white, raised, sometimes verrucous patches and may be precursor of VLS-associated SCC .

Treatment

UPTCS or potent TCS are the mainstay treatment of VLS . A first-line tapering schedule consists in administering clobetasol propionate 0.05% once a day for 1 month, every other day for 1 month and twice a week for 1 month . Then, there is no specific recommendation: some experts use a maintenance therapy for 1 to several years (a twice-a-week application of clobetasol propionate or a less potent corticosteroid such as betamethasone dipropionate), whereas others advise their patients to apply TCS ‘as required’. Symptoms are controlled within a few days or weeks, whereas pallor and atrophy respond more slowly, not always completely. Scarring, however, is not reversible. The side effects of TCS are rare ( Table 3 ).

Although ‘resistance’ usually witnesses for a benign-associated condition or for a lack of compliance, it may also reveal a neoplastic change: SCC or a precursor ( Table 4 ). True resistance to TCS is exceptional.

Pimecrolimus, a topical calcineurin inhibitor, is as effective as clobetasol in improving symptoms but less effective for improving the gross appearance of VLS . Topical calcineurin inhibitors are not recommended as a first-line treatment because their tolerance may be poor and because there are concerns about the risk of neoplasia when treating a potentially premalignant dermatosis . They could be offered, exceptionally, in case of resistance to TCS ( Table 4 ).

Indications for surgery are rare: correction of posterior labial adhesions in the case of dyspareunia, excision of a symptomatic epidermoid clitoral cyst and excision of areas of resistance to UPTCS.

Epidemiology

The prevalence of vulvar lichen planus (VLP) in the general population is unknown. Of women with oral LP, 19–67% have vulvovaginal disease . VLP mainly affects women between 40 and 60 and exceptionally occurs in girls .

Aetiology

LP is considered as an immunologically mediated condition involving T cells directed against the basal keratinocytes. This reaction is triggered by a yet unidentified antigen on a genetically predisposed background. This antigen might be a self-antigen or an exogenous antigen . Like for LS, an autoimmune aetiology of LP is supported by the association with autoimmune disorders, family history of autoimmunity and circulating organ-specific antibodies. A study of 126 women with adult-onset VLP found that autoimmune conditions, mainly thyroid disease, were significantly more frequent in patients with VLP than in examined controls (29% and 11.8% with at least one autoimmune disorder, respectively) . Anti-membrane-zone antibodies chiefly targeting BP180 are present in 61% of erosive LP sera, also suggesting that autoimmune mechanisms may be important in its pathogenesis .

The association between LP and hepatitis C has been also studied but the results are contradictory. Although more frequent in Mediterranean countries, in Japan and in USA, the association LP/hepatitis C cannot only be explained by geographical distribution. No association between hepatitis C and vulvar LP was found in 100 patients from the UK . A retrospective study including 141 patients showed a significant association of VLP with beta blockers and nonsteroidal anti inflammatory drugs. Withdrawal of these drugs should be considered in the case of VLP being resistant to the usual treatments . The clinical and pathological mucocutaneous features of chronic graft versus host (GVH) disease are indistinguishable from those of erosive LP .

Pathology

In active lesions of LP, the epidermis is typically hyperkeratotic, either acanthotic or atrophic or absent in the case of erosive LP. A characteristic feature is basal cell liquefactive degeneration associated with eosinophilic bodies in the basal epithelium and the papillary dermis. A dense band-like lymphohistiocytic infiltrate occupies the upper dermis and obscures the dermo-epidermal junction. Pigmentary incontinence is common. In burnt-out stages, the histopathology may be non-specific.

Symptoms

VLP may be asymptomatic or responsible for soreness, burning, pruritus or dyspareunia .

Signs

The morphological features of VLP may be divided into three categories which may be associated: classical papulosquamous, erosive–atrophic (EAVLP) or hypertrophic. EAVLP is the most common form of reported VLP accounting for 85% of the cases in a UK dermatological vulval clinic . The lesions consist of well-delimited red erosive or atrophic areas mainly located on the vestibule, the inner side of the labia minora and the clitoris ( Fig. 3 ). Architectural modifications resulting from interlabial or clitoral adhesions are similar to those observed in VLS. Erosive LP is frequently a multicentric condition which may have serious consequences on the quality of life. Vaginal involvement is frequently associated with EAVLP, as shown in a Norwegian vulvar clinic where it was detected in 49 of 58 cases (84.4%) . Patients are asymptomatic or complain from a chronic yellow discharge, severe dyspareunia and post-coital bleeding. Vaginal examination is painful and may provoke bleeding; erythema and erosions are often associated with adhesions. Vulvovaginal–gingival syndrome has been individualized as a subset of erosive LP . In addition to the vagina and mouth, other sites may be involved by erosive or non-erosive LP in patients with EAVLP. On the skin, LP is characterized by a symmetrical rash of pruritic, purple, polygonal flat-topped and shiny small papules involving preferentially the flexor aspects of the wrists, forearms, extensor aspects of the ankles and hands and the lumbar area. Scalp lesions were observed in 19.2% of 83 new patients with erosive VLP in a UK vulvar clinic and consisted of either diffuse, patchy or, most frequently, frontal scarring alopecia (50%) . Erosive LP may rarely involve the oesophagus (mainly the upper third) and should be suspected in the case of dysphagia in patients with EAVLP . The histology is frequently non-specific. Perforation or malignant transformation may occur. Otic and ocular LP are rarely associated with erosive VLP .

Vulvar Lichen Planus: well delimited atrophic red vestibular patches, scarring (loss of labia minora, sealing of the clitoris).

Non-erosive non-atrophic classical LP patterns are less frequently observed on the vulva and are usually associated with erosive–atrophic lesions. White, reticulate, lacy or fern-like striae are similar to those occurring on the oral mucosa. A uniform whitening simulates VLS. Hypertrophic VLP is rare accounting for 4% of a UK cohort . It presents as single or multiple white raised plaques.

Differential diagnosis

The main differential diagnoses of VLP are listed in Table 5 .

Diagnostic assessment

The diagnosis of VLP mainly relies on vulvar examination and search for extravulvar LP manifestations. Histology aims to confirm the diagnosis and to exclude neoplastic disorders (VIN, Paget’s disease and squamous cell carcinoma). A non-specific vulvar histology does not exclude the diagnosis of VLP. Indirect and direct immunofluorescence are indicated to exclude an autoimmune blistering disorder.

Evolution

VLP is a chronic condition, with an unpredictable relapsing and remitting course. Transformation into squamous cell carcinoma, although rare, is fully documented and mainly occurs in erosive VLP. In a prospective cohort study with a mean period of treatment and follow-up of 72 months, one of 114 adults with erosive VLP (0.8%) developed a vulvar squamous cell carcinoma, while two other patients had an oral and a perianal SCC, respectively . It is likely that VLP, like VLS, does not directly turn into SCC and that a precursor stage is necessary (differentiated VIN, acanthotic LP or usual VIN) . Precursor lesions or squamous cell carcinoma (SCC) should be suspected in the case of focal resistance to UPTCS such as white plaques and indurated or granulated ulcers.

Treatment

Evidence-based data on the treatment of VLP are limited and management choices mainly rely on clinical experience . UPTCS are the usual first-line treatment of VLP . The schedule is similar to those of VLS (see VLS). Persistence or reappearance of symptoms or signs in patients treated with UPTCS is more frequently related to an associated condition ( Table 4 ) than to a true resistance to UPTCS requiring another therapeutical option. In the case of resistance to UPTCS, calcineurin inhibitors may be offered . In the case of resistance to both UPTCS and calcineurin inhibitors, several systemic treatments such as systemic corticosteroids, methotrexate and retinoids have been used with no evidence that their benefits outweigh their risks . Vaginal LP is more difficult to control than VLP. Erosive lesions may respond to TCS whereas vaginal (as well as vulvar) adhesions are not reversible and may require surgical lysis if the patient is willing to have sexual intercourse . A close post-operative follow-up is required including TCS, the regular use of a vaginal dilators and sexual counselling.

Epidemiology, physiopathology

Lichen simplex chronicus (LSC) is one of the most common causes of vulvar itch. Primary LSC tends to appear in patients with an atopic diathesis. In these patients, the initial pruritus can be provoked by tight clothing, overcleaning or any irritant contact. Rubbing and scratching relieve the discomfort but damage the protective cutaneous barrier and contributes to thicken the epidermis and perpetuate the lesions. This vicious circle of itch–scratch–itch defines LSC. In secondary LSC, this vicious circle is initiated by an underlying vulvar condition such as contact dermatitis or psoriasis. Stress, heat, sweating and friction usually increase the itch leading to scratching.

Pathology

Histology shows hyperkeratosis, parakeratosis, acanthosis, a prominent granular layer, lengthened rete ridges and a variable chronic inflammatory infiltrate. There is lamellar thickening of the papillary dermis and sometimes perineural fibrosis. In secondary LSC, the specific features of the triggering dermatosis may be observed.

Symptoms

The main symptom is a chronic or intermittent pruritus occurring preferentially in the evening or during the night. Erosions related to scratching are responsible for burning and soreness.

Clinical features physiopathology

LSC most often affects the hair-bearing portion of the labia majora. The skin is thickened, erythematous, pale or pigmented, with accentuated skin markings secondary to rubbing. Linear excoriations witness for the scratching ( Fig. 4 ). Hair may be broken secondary to friction. Full cutaneous examination is aimed to find clues for an aetiological dermatosis.

Lichen Simplex Chronicus: thickening of the right labium majus with accentuated skin markings.

Diagnosis assessment–differential diagnosis

The diagnosis is usually straightforward. However, psoriasis or more rarely vulvar intraepithelial neoplasia, Paget’s disease, dermatophytosis and Streptococcus A infection may mimic LSC. Specific clinical vulvar or extra vulvar features of each condition as well as pathology and bacterial or fungal specimens are indicated in the case of resistance to treatment.

Evolution

LSC is a chronic condition with relapsing and remitting phases. LSC is not associated with a risk of SCC.

Treatment

There are no evidence-based data concerning the treatment of LSC. However, most of the experts use potent or ultrapotent topical steroid to treat LSC, and recommend avoiding irritants and regularly moisturizing the skin. The treatment of an underlying dermatosis is indicated in the case of secondary LSC.

Potent or ultrapotent topical steroids applied once a day for 3–4 weeks rapidly control the itch, decrease inflammation and break the itch–scratch cycle. Some experts use a tapering schedule or switch to a weaker topical steroid for 3–6 months in order to prevent relapse. Others advise the patient to apply corticosteroids ‘as required’ . Due to the quick effect of TCS, topical anaesthetics or antihistamines are usually not required to control itching.

Topical calcineurin inhibitors (pimecrolimus 1% cream and tacrolimus ointment) are used as a secondary-line treatment for the very rare patients who are intolerant or resistant to TCS (tapering schedule starting with applications once or twice a day for 6 weeks) . These topics may provoke irritation.

Epidemiology

The prevalence of vulvar contact dermatitis in the general population is unknown. In a vulvar clinic in Oxford and in Australia, 20–30% and 15% of the patients, were considered to have allergic or irritant dermatitis, respectively .

Aetiology

Contact dermatitis is an inflammation provoked by an external agent acting as an irritant or an allergen. Contact dermatitis can complicate the topical treatment of a pre-existing vulvar condition.

Irritant contact dermatitis is more common than allergic contact dermatitis. Irritation results from a loss of the barrier function related to moisture, enzymes, friction, heat and oestrogen deficiency. Urinary incontinence is probably one of the main causes of irritant dermatitis. Allergic contact dermatitis is an immunologically mediated inflammatory cutaneous reaction (type IV hypersensitivity) to an allergen in a sensitized individual. Different allergens have been reported in patients with vulvar complaints, mainly topical anaesthetics (benzocaine and lidocaine), nickel, neomycin, perfume and corticosteroids.

Pathology

Spongiosis, acanthosis, parakeratosis and dermal inflammatory infiltrate are the histological hallmarks of vulvar contact dermatitis.

Symptoms

Patients with irritant or allergic contact dermatitis both mainly suffer from acute or chronic pruritus or burning.

Clinical features

In acute vulvar dermatitis, there is an ill-defined erythema diversely associated with swelling, oozing, vesicles or erosions. Ulcers or papulonodular ulcerated lesions are observed in irritant dermatitis only either in children, on the napkin area or in the case of urinary incontinence in the elderly.

In chronic cases, lichenification, excoriations and hyper- or hypopigmentation are observed. Superimposed bacterial infection should be suspected in the case of pustules, crusting and fissuring.

Diagnosis assessment

A careful history should be taken to search for incontinence and for any application of potentially irritant or allergenic product applied on the vulva or on the hands.

Anamnesis and inspection are usually sufficient to make the diagnosis of irritant dermatitis (incontinence, obvious use of irritant products or inappropriate hygiene habits). The diagnosis of allergic contact vulvitis is more difficult to assess. Patch tests, classically applied on the back, do not reproduce the environment of the vulva. On the other hand, a positive patch test should be interpreted with caution as it could be non-relevant . For both allergic and irritant contact vulvitis, remission after withdrawal of the suspected agent does not mandatorily confirm its responsibility. Only reintroduction could confirm the diagnosis: however, this test is rarely done and, finally, the diagnosis of contact vulvitis, particularly allergic dermatitis is frequently suspected but rarely confirmed.

Biopsy helps exclude differential diagnosis and can only conclude to histological features ‘compatible’ with the diagnosis of allergic or irritant vulvitis.

Differential diagnosis

Differential diagnosis mainly include vulvo-vaginal candidiasis, Streptococcus A infection, psoriasis, LSC and Paget’s disease.

Evolution

The evolution depends on the contacts with the irritant or allergic products. Complete remission is expected if these products are withdrawn.

Treatment

The treatment of contact vulvitis consists in eradicating the offending agent or changing inappropriate hygiene habits. TCS help rapidly control itching and inflammation. Moisturizing the vulva by a non-irritant cream such as petrolatum and prescribing hydroxyzine or doxepin to control the itching may be helpful.